Our study reveals that the frequency of neoadjuvant MRI was greater in younger patients with dense breast tissue and multifocal disease. In the population of patients with known early-stage breast cancer, MRI was most frequently indicated to better delineate disease extent. Additionally, our study is the first to report the clinical utility of neoadjuvant MRI, specifically with regard to how MRI aided conventional imaging in further evaluation of tumor multifocality, multicentricity, nodal involvement and contralateral breast findings. Ultimately, the identification of these findings by MRI resulted in frequent additional diagnostic interventions and more frequent alterations to surgical management plans for the breast and axilla, with higher rates of mastectomies and axillary dissections.
The fact that MRI use was more frequently used in a younger patient population is consistent with previously published data. Traditionally, MRI has been proposed as an additional screening test for younger women at high risk of breast cancer or those with a germline mutation in the BRCA1 or BRCA2 genes in whom mammography alone has lower sensitivity [12]. Additionally, MRI is more frequently recommended for younger women due to increased breast density in this patient population [26]. Given that BI-RADS has only recently been mandated for mammographic reports in BC, this information was unavailable in more than half of the patients included in this study, limiting the generalizability of these findings. Nevertheless, a higher density of breast tissue has been generally accepted as an indication for MRI [22], partially due to better fat suppression and a higher resolution [14]. This is particularly relevant prior to NAT where disease extent and accurate staging are utilized for assessment of treatment response and locoregional treatment planning [24]. Additionally, while there are no clear guidelines on who should receive an MRI in neoadjuvant settings, the most frequent reason for an MRI was to better delineate disease extent, which is consistent with earlier reports [4–5, 9, 17]. Although not adopted as a standard-of-care, MRI prior to NAT is being increasingly used for the evaluation disease extent and the prediction of NAT response [24].
Our analyses demonstrated that discrepancies between clinical and radiological staging were frequent and noted in 73% of patients. To our knowledge, no prior study has directly correlated the findings between other conventional imaging, clinical extent of disease and MRI in the pre-operative setting. However, in keeping with these findings, DeMartini and colleagues summarized the results of multiple studies that collectively evaluated MRI in approximately 1,500 cases of newly diagnosed breast cancer. All found that MRI identified additional ipsilateral malignancy with a reported frequency that ranged from 10%-34% [5]. In another meta-analysis, MRI reported additional contralateral cancers in 4% of subjects [2]. One of the significant issues associated with breast MRI is the high rate of false-positive findings which overestimates the extent of the disease and can result in additional investigations, unnecessary biopsies, and more extensive surgery [1, 10]. Our study found that just over half of the patients who underwent MRI were subjected to additional investigations. Rates of false-positive MRI findings were not evaluated as part of this study; however, the existing literature reports the false-positive rates ranging from 29–80% [10].
With regard to changes in surgical management, surgical plans for the breast and axilla were altered in nearly 27% and 28% of cases, respectively. In line with these findings, it’s been previously reported that 13-26% of women with invasive breast cancer have a change in surgical management based on pre-operative MRI evaluation and 7-17% alter their surgical treatment from lumpectomy to mastectomy [10]. Chen and colleagues also conducted a systematic analysis to investigate how pre- and post-NAC MRI findings affect the surgeon’s recommendation [3]. They concluded that tumor size, multifocality, and disease extent on pre-treatment MRI indeed affected the initial surgical recommendation (mastectomy versus lumpectomy). However, it remains unclear that additional surgery results in lower rates of local, regional and distant relapses. While our study was not powered to detect these detect small differences, no significant differences were noted with the exploratory analyses.
Amongst the limitations, it should be noted that this was a non-randomized cohort study with a retrospective analysis of a prospective database. Additional information that was not accounted for could have impacted the frequency of changes in surgical management. Patient specific factors, such as increased anxiety [11], more extensive MRI findings than anticipated and patients seeking reconstruction for cosmesis or balancing surgery [20], may have contributed to the higher rates of change in surgical planning. We did not directly investigate if additional MRI findings and patterns of MRI use added any benefit to long-term outcomes in the studied patient population given short follow-up data, but this will be examined when longer follow-up has been established. Furthermore, a number of questions remain unanswered, including the impact of neoadjuvant MRI on the frequency of positive margins, cancer recurrence and mortality, given that data to date have not clearly established the benefits of MRI on rates of reoperation, disease recurrence, or survival [19]. To this effect, a prospectively designed trial is underway at BC Cancer in an attempt to shed light of some of these unanswered questions (NCT03790813). The results of the current study can be used to design future prospective trials to better capture the extent to which MRI findings impact intended treatment, to define the subpopulation of patients with the highest benefit from MRI, and to establish appropriate guidelines for recommending MRI prior to NAT.